Autologous Adipose-Derived MSCs for Chronic Traumatic Brain Injury
Abstract
This project seeks to develop a treatment for the long?term after?effects of severe traumatic brain injury. Severe traumatic brain injury acutely results in coma, and about 50% of patients with severe traumatic brain injury have a bad outcome (defined as death, vegetative state or severe disability). The other 50% improve, but most are left with functional deficits from the injury. The long-term after?effects are mediated, at least in part, by immune cells within the brain that are chronically activated; many studies have linked the chronic inflammation to neurodegenerative processes that cause the loss of brain tissue over time and worse functional outcomes. We have studied the use of a specific cell type (mesenchymal stromal cells) derived from a patient’s adipose tissue to reduce the chronic immune activation. We have studied the use of the cells in animal models of severe TBI, and we have recently completed enrollment in a Phase 1 clinical trial of patients with chronic after?effects of severe TBI. In this study, there was a reduction in immune activation noted using advanced brain imaging techniques called PET?MRI. The objective of this proposal is to further these observations in a blinded manner (neither we nor the patients know whether they get the treatment or not) to add rigor to the experimental design. Patients with chronic after?effects of TBI will receive either an infusion of adipose derived MSCs (derived from their own tissue) or a placebo. All patients will undergo a battery of neurocognitive and functional testing as well as advanced imaging that measures the degree of inflammation in the brain and the location of the inflammation. These tests will be completed before the infusions (3 doses, 2 weeks apart) and at 6 months after the infusions. When the study is completed, the information will be analyzed by the groups and then unmasked. We plan a 6-month planning phase, during which we will ensure the two sites have harmonized all procedures for the trial. Likewise, we will engage a CBPR panel to inform us on final logistical and practical issues of the clinical trial: access and enrollment, patient centric outcome measures, and more effective informed consent. This research addresses the discrete Treatment focus area of the FY22 TBIPHRP CTA Focus Area. The impact of this work will be to potentially improve functional outcomes in patients suffering from cognitive and functional deficits after a severe TBI. The patients will be recruited from both civilian and VA populations in Houston and San Antonio, Texas. Ultimately, the potential clinical application and benefit would be for patients who have reached a plateau in their recovery from TBI and augment their functional recovery. The treatment has proven safe with few risks. There is a theoretic risk of increased venous thromboembolism (blood clots), which has not been borne out in our safety study. Further, we reduce that risk by treating with a mild anticoagulant for 5 days around the treatment window. The trial will take place over a period of 3 years, and each individual patient would be expected to achieve any outcome by 6 months post?treatment. If successful, the proposed project will improve the functional outcomes of injured patients and offer a treatment for a problem for which no current restorative treatment exists.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310991
Entities
People
- C. E. Cox
Organizations
- United States Army
- University of Texas Health Science Center at Houston